Imbruvica (ibrutinib) is only moderately effective against tumors in patients with relapsed follicular lymphoma, and certain clinical and genetic factors may have an impact on patient response, according to results from a Phase 2 clinical trial.

Specifically, researchers found that patients who did not previously respond to Rituxan (rituximab) and those with mutations in the CARD11 gene are less likely to see results from Imbruvica.

Imbruvica, an irreversible Bruton’s tyrosine kinase (BTK) inhibitor, works by blocking the activity of BTK, a protein that helps B-cells stay alive and divide, aiding in killing or reducing cancerous B-cells.

It is an oral therapy approved for treatment of many B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia. Imbruvica was also recently approved for the treatment of chronic graft-versus-host disease.

The drug showed promising results in a Phase 1 trial (NCT00849654) for patients with relapsed follicular lymphoma. The medicine was well-tolerated and was found to reduce tumors in 54% of patients who received at least a 2.5 mg/kg dose per day.

Building on the Phase 1 data, a Phase 2 trial (NCT01849263) was set up to address how well Imbruvica works in treating follicular lymphoma patients who relapsed or did not respond at all to previous treatment.

Forty patients received 560 mg of Imbruvica once a day, until the therapy wasn’t tolerated or the disease progressed. Response to treatment was measured as tumor reduction determined by computed tomography (CT) scans.

After a median follow-up at 25.5 months, 37.5% of patients saw reductions in their tumors. Five patients (12.5%) had no signs of cancer, as determined by CT scans and a negative bone marrow biopsy.

Patients who responded remained alive and progression-free for a median of 14 months. At two years, 79% of patients were still alive.

Researchers examined several factors to identify which patients saw better results with Imbruvica.

They found that patients who had previously responded to Rituxan had better response rates, compared to those who were Rituxan-resistant — 52.6% vs. 16.7%.

The team also showed that early PET/CT scan results eight days after starting Imbruvica corresponded with both overall response rates and progression-free survival in those with less active tumors. Patients with brighter scans — showing the imaging agent was taken up by more cancer cells — showed worse results.

This supports the use of PET scans, which are not typically used for managing patients with follicular lymphoma, as important tools to predict treatment responses.

An analysis of tumor samples collected before the start of Imbruvica therapy also showed that patients with mutations in the CARD11 gene did not respond to the medicine.

As noted earlier, Imbruvica was generally well-tolerated with a toxicity profile similar to labeled indications.

“The favorable AE [adverse effect] profile in most patients, particularly the lack of myelosuppression, may be beneficial in patients who will require multiple future lines of therapy,” the researchers said.

The study shows that the therapy alone offers only moderate results for the treatment of relapsed or refractory follicular lymphoma patients. But given the higher response rates in patients sensitive to Rituxan, the researchers say that future studies assessing the effect of Imbruvica in earlier lines of therapy might be warranted.

Lymphoma News Today

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